Pemphigus vulgaris is a rare, potentially fatal, autoimmune blistering disease of the skin and mucous membranes. Treatment of this disease is problematic because of a lack of high-grade, evidence-based recommendations, the side-effect profiles of the therapies available, and the extensive supportive care that afflicted patients require. The authors present the unfortunate course of a patient with severe pemphigus vulgaris who was admitted to the U.S. Army Institute of Surgical Research Burn Center, to demonstrate the potential complications of therapy. Given the patient’s complex course, the authors reviewed the literature and share in this article the most up-to-date treatment recommendations for patients with pemphigus vulgaris. The authors’ review of the literature supports using conventional therapy consisting of high-dose corticosteroids and an adjuvant immunosuppressant for mild to moderate cases of pemphigus vulgaris. The immunosuppresants recommended are mycophenolate mofetil, azathioprine, and cyclophosphamide, in order of preference, based on their side-effect profiles and steroid-sparing effects. For severe or recalcitrant cases of pemphigus vulgaris, the authors recommend adding rituximab as early as possible. If increased risk of infection is of particular concern, the use of intravenous immunoglobulin in place of rituximab is advised.